Si. Danto et al., REVERSIBLE TRANSDIFFERENTIATION OF ALVEOLAR EPITHELIAL-CELLS, American journal of respiratory cell and molecular biology, 12(5), 1995, pp. 497-502
Alveolar epithelial type II (AT2) cells have been thought to be the pr
ogenitors of terminally differentiated type I (AT1) cells in the adult
animal in vivo. In this study, we used an AT1 cell-specific monoclona
l antibody (mAb VIII B2) to investigate expression of the An cell phen
otype accompanying reversible changes in expression of the AT2 cell ph
enotype. AT2 cells were isolated and cultured either on attached colla
gen gels or on gels detached 1 or 4 days after plating and maintained
thereafter as floating gels. Monolayers on both attached and floating
gels were harvested on days 4 and 8 and analyzed by electron microscop
y for changes in morphology and binding of mAb VIII B2. Results indica
te that: (1) alveolar epithelial cells (AEC) on attached gels develop
characteristics of the AT1 cell phenotype, (2) AEC on gels detached on
day 1 maintain features of the AT2 cell phenotype (and do not react w
ith mAb VIII B2), and (3) the expression of ATI cell phenotypic traits
seen by day 4 on attached gels is reversed after detachment. We concl
ude that commitment to the AT1 and AT2 cell lineages requires continuo
us regulatory input to maintain the differentiated states, and that tr
ansdifferentiation between AT2 and AT1 cells may be reversible.